Lysosomal dysfunction is emerging as a common pathogenic mechanism underlying normal ageing and many age-related diseases. Lysohormesis, the triggering of beneficial adaptations by mild lysosomal stress leading to increased lysosomal function and cellular stress resilience, could provide a common solution to many age-related issues.

This Review discusses the recent advances in experimental approaches to interrogate the mechanical forces that mediate tissue deformations during development, highlighting the insights afforded at both the cellular and tissue scales.

Auwerx and colleagues review recent advances in mitochondrial genetics, proteomics and biochemistry that emphasize the far-reaching impact of mitochondrial genetic variation and the role of mitochondria as finely tuned signalling hubs.

This Perspective discusses the various biases that can emerge along the pipeline of machine learning-based single-cell analysis and presents methods to train models on human single-cell data in order to assess and mitigate these biases.

Rettkowski, Romero-Mulero et al. show that myocardial infarction impacts bone marrow haematopoietic stem cells and leads to inflammatory myelopoiesis, which can be dampened by treatment with 4-oxo-retinoic acid, promoting cardiac recovery.

Chou et al. generate transdifferentiated human neurons from fibroblasts from young or aged individuals and patients with Alzheimer’s disease. Studies of endolysosomes and proteostasis suggest a role for lysosomal quality control in Alzheimer’s disease pathology.

Lange, Ratz, et al. investigate the number and distribution of human prohibitin complexes in the mitochondrial inner membrane, uncovering their bell-shaped structure and assembly of alternating PHB1 and PHB2 molecules.

Sun et al. identify a role for PABPC1 in selectively regulating the translation of leukaemogenic mRNAs to promote blast crisis transition, which may be targeted to overcome resistance to TKI treatment in chronic myeloid leukaemia.

Fan et al. report a role for PRMT5 in regulating GPX4 stability and ferroptosis sensitivity through arginine methylation, which may be targeted to inhibit tumour development.

Duan, Hu, Han, Lei, Wang et al. report that ADSL-mediated production of fumarate suppresses STING activation and impairs T cell and NK cell infiltration, thereby facilitating immune evasion in breast cancer.

Lysosomal dysfunction is emerging as a common pathogenic mechanism underlying normal ageing and many age-related diseases. Lysohormesis, the triggering of beneficial adaptations by mild lysosomal stress leading to increased lysosomal function and cellular stress resilience, could provide a common solution to many age-related issues.